Disposable syringe for use with pneumatic drivers

ABSTRACT

A disposable syringe for use with a pneumatic driver. The syringe has an elongated barrel with a cap secured to the proximal end that has a through bore. A filter is secured to the cap interior of the barrel that covers an opening in the through bore interior of the barrel. The pneumatic driver includes a source of pressurized air; a support for receiving and locating the syringe; and a supply block configured to receive pressurized air from the source and having an outlet for delivery of pressurized air. The supply block is movable between a first position spaced apart from the cap of the syringe and a second position in contact with the cap with fluid communication being established between the outlet of the supply block and the through-bore in the cap.

TECHNICAL FIELD

The present disclosure is directed broadly to systems and methods forwashing suspensions of biological cells. More particularly, the presentdisclosure is directed to systems and methods for washing small volumesof biological cells utilizing syringes actuated by pneumatic drivers foreffecting movement of fluid through the system.

BACKGROUND

A number of well-known therapies are currently practiced in which atargeted cellular blood component (e.g., red blood cells, white bloodcells, and platelets) is separated from whole blood and stored for laterinfusion to a patient. The targeted cellular product (e.g., red bloodcells or platelets) may be in a suspension that includes plasma and/orsome other supernatant. As such, it is sometimes desirable to “wash” thecellular suspension (typically with saline) to remove theplasma/supernatant, as well as any non-target cellular material, priorto reinfusion.

Systems and methods for cell washing are exemplified by US 2013/0341291,US 2013/0092630, and US 2014/0199680, each of which is incorporatedherein by reference. Each of these published applications discloses cellwashing methods utilizing systems and fluid circuits including aspinning membrane separator. Such systems include peristaltic pumps andpinch valves that act on tubing to direct flow within the fluid circuit.

The fluid circuits in the cited published applications have a relativelylarge internal volume, and thus require relatively large volumes of washor flush media to clear processed fluid through the fluid circuit. Whilesuch systems and fluid circuits are capable of washing and reducing thevolume of the targeted cellular component into final volumes of rangingfrom approximately 50 mL to 5,000 mL, there are instances in whichsmaller final volumes (e.g., 10 mL) are desired, such as when processingsingle-dose quantities of mononuclear cell products. A system and methodfor washing small volumes of cells is shown in US 2017/0204371, which isincorporated herein by reference.

More specifically, US 2017/0204371 discloses a fluid circuit for cellwashing that comprises a spinning membrane separator and a fluidmanagement system comprising a cassette. The cassette defines the fluidpathways, and includes internally mechanical valving, pressure sensingand air sensing for controlling flow through the fluid pathways.Additionally, the fluid circuit comprises syringes that are acted on bysyringe pumps or drivers that are associated with the hardware componentof the system to move the stoppers of the syringes within the syringebarrel, and thus provide pressure for moving fluid through the circuit.

US 2018/0155070, which is also incorporated by reference herein,discloses a variety of options for filling a cell product into acontainer, including end user containers, in which the container maytake the form of a syringe. A vacuum/pressure source is associated withthe syringe to move the plunger head assembly within the barrel of thesyringe. Positional sensors provide signals indicative of the locationof the stopper within the syringe barrel

During various stages of a washing procedure, such as that contemplatedby US 2017/0204371, and a fill procedure, such as that contemplated byUS 2018/0155070, suspensions of biological cells, supernatant and thelike are drawn into and discharged from the barrels of the syringes.Thus, it is important to maintain the sterility of the syringes, whileat the same time providing for efficient and controlled movement of thecell suspension through the system.

By way of the present application, a syringe and a pneumatic syringedriver are provided in which the pneumatic driver includes structurethat locates and supports the syringe, and sealingly engages the syringeso that the stopper of the syringe can be driven without breakingsterility and opening the system.

SUMMARY

The present application has several aspects. In a first aspect, adisposable syringe is provided comprising an elongated tubular barrelhaving a first end and a second end, the barrel being open on the firstend and tapering to a hollow tip on the second end; a cap secured to thefirst end of the barrel having a through-bore; a filter secured to thecap interior of the barrel and covering an opening in the through boreinterior of the barrel; and a plunger head mounted to a piston andreceived interior of the barrel, the plunger head engaging an interiorwall of the barrel and being slidable within the barrel between thefirst and second ends.

In a second aspect, the barrel of the syringe further comprises a collarat the first end that extends laterally from the barrel, and the cap ismounted to the collar.

In a third aspect, the tip of the syringe further comprises a luer lock.

In a fourth aspect, the through-bore in the cap of the syringe isconfigured to receive the tip of a second syringe.

In a fifth aspect, the cap of the syringe further comprises a luer lockextending exterior of the barrel and defining an exterior opening in thethrough-bore.

In a sixth aspect, the filter of the syringe is configured to form aluer lock.

In a seventh aspect, the piston of the syringe further comprises ahollow interior configured to receive the luer lock formed by thefilter.

In an eighth aspect, the barrel of the syringe further comprises anannular, inwardly-projecting ridge adjacent the first end for sealinglyengaging the cap.

In a ninth aspect, the cap of the syringe comprises an annular,radially-projecting seal for engaging the circumferential,inwardly-projecting ridge at the first end of the barrel.

In a tenth aspect, the syringe further comprises a gasket secured to thepiston for engaging the interior wall of the barrel.

In an eleventh aspect, the cap of the syringe is removably secured tothe barrel.

In a twelfth aspect, the cap of the syringe further comprises a sealencircling an opening in the through bore exterior to the barrel.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side view, in partial cross section, of a pneumatic driverin combination with a disposable syringe, with the pneumatic driver inthe open position, in accordance with the present application.

FIG. 2 is a side view, in partial cross section, of the pneumatic driverin combination with a disposable syringe, with the pneumatic driver inthe closed position.

FIG. 3 is a side view, in partial cross section, of the pneumaticdriver, with the pneumatic driver in the open position.

FIG. 4 is a side view, in partial cross section, of the pneumaticdriver, with the pneumatic driver in the closed position.

FIG. 5 is a front view of the pneumatic driver in combination with adisposable syringe, with the pneumatic driver in the closed position.

FIG. 6 is an enlarged fragmentary front view of the pneumatic driver incombination with a disposable syringe, with the pneumatic driver in theclosed position.

FIG. 7 is a rear view of the pneumatic driver.

FIG. 8 is a top view of the pneumatic driver, with the cover removed forclarity.

FIG. 9 is an enlarged fragmentary perspective view of the pneumaticdriver in combination with a disposable syringe, with the pneumaticdriver in the open position.

FIG. 10 is an enlarged fragmentary view of an alternate embodiment foran over-center latching assembly for moving the pneumatic driver intoand out of sealing engagement with an associated disposable syringe.

FIG. 11 is an enlarged fragmentary cross sectional view of the upper orproximal end of a disposable syringe in accordance with the presentapplication.

FIG. 12 is a cross-sectional view of an alternative embodiment of theassembly of the syringe cap and filter.

FIG. 13 is an enlarged cross-sectional view of further alternativeconfiguration of the syringe cap.

FIG. 14 is a cross sectional view of the stopper received in the barrelof the syringe.

FIG. 15 is a schematic view of a disposable processing set that includeselongated syringe barrels of the type that would be used with thepneumatic driver of the present disclosure.

FIG. 16 is an enlarged view of a flow control cassette forming part ofthe disposable processing set of FIG. 15.

DETAILED DESCRIPTION

A more detailed description of the systems and methods in accordancewith the present disclosure is set forth below. It should be understoodthat the description below of specific devices and methods is intendedto be exemplary, and not exhaustive of all possible variations orapplications. Thus, the scope of the disclosure is not intended to belimiting, and should be understood to encompass variations orembodiments that would occur to persons of ordinary skill.

Turning to the drawings, a pneumatic syringe driver or actuator 10 isshown which may be used in combination with a disposable syringe 12. Asis typical of a standard syringe, the syringe generally comprises anelongated barrel 14 having a first or proximal end and a second ordistal end. The barrel is open on the first end and terminates in ahollow tip on the second end. The tip of the syringe may further beconfigured to comprise a luer lock 16.

The elongated barrel 14 of the syringe is preferably incorporated into adisposable processing set. A representative processing set 90 is shownin FIG. 15. With reference to FIG. 15, the disposable processing set 90includes two elongated syringe barrels 92, 94, with elongated barrel 92for the syringe that provides the motive force for the retentate, andthe elongated barrel 94 for the syringe that provides the motive forcefor the filtrate.

The disposable processing set 90 also includes a flow control cassette96, best seen in FIG. 16. The flow control cassette 96 has a pluralityof passageways 98 defined on the interior thereof that are in fluidcommunication with various of a plurality of ports 100, 102, 104, 106,108, 110, 112, 114, 116, 118, 120, 122 on the exterior wall of thecassette 96. The outlets of the elongated syringe barrels 92, 94 arerespectively connected by a tubing segment to ports 100, 102. Ports 104,106 and 108 respectively connect the inlet, the retentate outlet and thefiltrate outlet of a spinning membrane separator 124 to the cassette.Port 110 connects to a tubing segment associated with a container/bag126 for receiving filtrate; port 112 connects to a tubing segmentassociated with one or more containers (not shown) of wash solution;port 114 connects to a tubing segment associated with a container (notshown) of an alternate solution depending on the application (e.g., thesolution could be a cryopreservation solution); port 116 connects to atubing segment associated with a source container (not shown); port 118connects to a tubing segment associated with a bulk suspension bag 128;port 120 connects to a tubing segment associated with a final productcontainer (not shown); and port 122 connects to a tubing segmentassociated with a vent 130. Various of the tubing segments are providedwith manual pinch clamps 132, such as Roberts' clamps.

Fluid flow through the cassette 96 is controlled by a series of valves134 that are opened and closed to selectively interconnect thepassageways 98. In addition, air detectors 136 associated with ports100, 102, 112, 114, and 116 of the cassette provide signals to aprogrammable controller that automatically opens and closes the valvesto direct fluid through passageways and ports of the cassette.

The pneumatic driver 10 includes an air supply block 18 that sealinglyengages the syringe 12 to introduce positive or negative air pressureinto the barrel 14 of the syringe. The positive and negative airpressure serve to repeatedly move the stopper 20 of the syringe axiallyback and forth within the barrel 14 to draw fluid into the syringe (withthe application of negative air pressure or a vacuum force) or to expelfluid from the barrel of the syringe (with the application of positiveair pressure).

The proximal end of the syringe barrel is provided with a cap 22 havinga through bore 24, through which pressurized air is introduced into thebarrel of the syringe by means of the air supply block 18. Preferably,the cap 22 is removably secured to the barrel 14 to permit post-useexamination of the cap 22, as described in greater detail below.

As illustrated, the barrel 14 of the syringe further comprises a collaror flanges 26 at the first end that extend laterally from the barrel(which typically provide a surface for grasping the syringe with theindex finger and middle finger), and the cap 22 is mounted to theflanges 26. Further, as illustrated, the barrel 14 of the syringe isformed with an annular, inwardly-projecting ridge 28 adjacent theproximal end for sealingly engaging an annular, radially-projecting sealor gasket 30 associated with the cap 22 (as best seen in FIG. 11).However, alternate sealing configurations are contemplated.

Generally speaking, the pneumatic driver or actuator 10 comprises asource of pressurized air 32. As illustrated, the pneumatic source 32comprises a compressor pump, but could alternatively comprise pressureand vacuum reservoirs or, possibly, a syringe or hand pump. The airsupply block 18 is configured to receive pressurized air from thepneumatic source 32 by means of a first set of tubes 34 that connect thepneumatic source 32 to a series of valves 36, and a second set of tubes37 that connect the valves 36 to a pressure sensor 38 (best seen in FIG.7) and to the air supply block 18. A programmable controller 39 ispreferably provided to automatically control air flow through the airflow pathway by turning the pneumatic source on and off and actuation ofthe valves 36 in response to signals received from the pressure sensor38, and or from sensors providing positional feedback for the stopper(e.g., as described in US 2018/0155070), time limits, or otherprogrammed behaviors.

The supply block 18 includes an outlet 40 for the delivery ofpressurized air to the barrel 14 of the syringe 12 through the throughbore 24 in the cap 22. To this end, the air supply block 18 is movablebetween a first position spaced apart from the cap 22 of the syringe(FIG. 1) and a second position in contact with the cap (FIG. 2), withfluid communication being established between the outlet 40 of thesupply block 18 and the through bore 24 in the cap 22.

A seal 42 is provided between the outlet 40 of the air supply block 18and the through-bore 24 in the cap 22 when the air supply block 18 is inthe second position. Preferably, the seal 42 comprises a resilientO-ring or other compliant gasket captured in the face of the air supplyblock. Alternatively, the top face of the cap 18 of the syringe couldinclude an O-ring seal or gasket that surrounds the inlet of the throughbore 20. The cavity defined by the O-ring or gasket 42 is larger thanthe inlet in the through bore 24, thus accommodating some misalignmentbetween the outlet of the air supply block and the inlet of the throughbore. The O-ring or gasket 42 also serves to provide some tactilefeedback as the air supply block 18 is brought into engagement with thecap 22, and further accommodates some planar misalignment between themating surfaces of the air supply block and the cap. Alternatively, theoutlet 40 of the air supply block 18 may comprises a luer fitting formating with a complementary luer fitting formed by the inlet of thethrough bore 24 in the cap 22. Further, the luer fittings may bethreaded and the supply block configured to be rotatable for couplingthe luer fitting of the air supply block with that of the cap.

As illustrated, the pneumatic actuator also comprises a base 44, towhich are mounted the source of pressurized air 32 and the air supplyblock 18. Also mounted to the base 44 is a support 46 that cooperateswith the cap 22 of the syringe 12 to mount the syringe 12 to theactuator 10, with the air supply block 18 defining a longitudinal axisgenerally aligned with the longitudinal axis of a syringe 10 received inthe support 46 when the air supply block is in the closed position.Preferably, the support 46 comprises a pair of arms that are spacedapart a distance sufficient to receive the barrel 14 of the syringetherebetween. The front or outer edges of the arms including a raisededge or shoulder 48 which serves to positively locate the cap 22 in thesupport 46.

The air supply block 18 is movably attached to the base 44 for movementbetween a first “open” position (to permit a syringe 12 to be loadedonto or removed from the support 46), and second “closed” position (inwhich the air supply block 18 is brought into sealing engagement withthe cap 22 of the syringe 14). To this end, the air supply block 18 ismounted to the base 44 by a plurality of links 50, each link 50 having afirst and second end. The first end of each link is pivotally secured toan adapter plate 44 a that is secured to the base 44 in a manner topermit the location of the adapter plate 44 a relative to the base 44 tobe adjusted. For example, the base 44 may include slots for receivingthreaded bolts that secure the adapter plate 44 a to the base so thatthe adapter plate may be moved relative to the base 44 along the slots.The second end of each link is pivotally secured to the air supply block18.

As illustrated, two pairs of links 50 are pivotally secured to the airsupply block 18 and the adapter plate 44 a, so that the links 50 of eachpair are substantially parallel throughout a range of motion from thefirst position to the second position. Such a four link assemblage iscommonly referred to as a “four-bar linkage.” The tolerances of the fourbar linkage assembly may be sufficiently loose to allow for any planarmisalignment between the air supply block 18 and the cap 22, while stillholding the syringe 12 securely. However, the tolerances should not beso loose as to permit the user to feel the looseness.

A lever 51 is provided for moving the air supply block 18 between theopen and closed positions. The lever 51 is pivotally attached to theadapter plate 44 a. A pair of further links 52 are provided, each link52 having first and second ends, with the first end of each link 52being pivotally secured to the lever 51 and the second end of the link52 being pivotally secured to the air supply block 18.

Movement of the lever 51 relative to the base 44 moves the air supplyblock 18 between the first, open position and the second closedposition. Preferably, when in the second, closed position, links 52 goover center to abut the adapter plate 44 a to act as a stop. Thus, thelever 51 and links 52 form an over-center latching mechanism.Consequently, a vertically upward force on the syringe 12 does not movethe air supply block 18, while an upward force applied directly to thelever 51 will cause the links 52 to move the air supply block to theopen position. As illustrated, the lever 51 is intended to be manuallyoperated by the user. However, this could be automated.

Preferably, a cover 53 is associated with the lever 51. The cover 53 isspaced away from the base when the supply block is in the first, openposition (FIG. 1) and is spaced closer to the base when the supply blockis in the second, closed position (FIG. 2), so as to shield the proximalend of the syringe when it is engaged by the air supply block 18.

Alternatively, and with reference to FIG. 10, a latch 54 may be providedfor moving the air supply block 18 between the first and secondpositions. The latch 54 is pivotally mounted relative to the base 44 andcomprises an arcuate track 56. A guide block 58 is secured to the base44 that comprises a linear track 60 that is generally aligned with thelongitudinal axis of the supply block 18. The air supply block 18further includes a follower 62 received in both the arcuate track 56 ofthe latch 54 and the linear track 60 of the guide block 58, such thatwhen the latch 54 is pivoted, the arcuate track engages 56 the follower62 to move the follower 62 along the linear track 60, and thus move theair supply block 18 between the first and second positions. Preferably,the arcuate and linear tracks 56, 60 are in the form of slots in thelatch and mounting block 54, 58, respectively, while the follower 62 isa pin forming part of the air supply block 18.

In order to maintain the air supply block 18 and lever/cover 50 in theopen position to facilitate the loading of a syringe onto the support,the pneumatic driver 10 further comprises a first permanent magnet 64secured to the base 44 and a second permanent magnet 66 secured to theair supply block 18. Preferably, the first magnet 64 is secured to theadapter plate 44 a, so that its position is adjustable. When the airsupply block 18 and lever/cover 50 are in the open position, the firstand second magnets 64, 66 are in sufficiently close proximity so thatthe force of attraction between the magnets maintains the air supplyblock 18 in the open position in the absence of a further external forcebeing applied to the air supply block 18 through the lever/cover 50. Themagnets 64, 66 also provide for tactile feedback of the cover being inthe open position.

Turning to the disposable syringe 12 that is part of the system, asdescribed above, the syringe 12 comprises a barrel 14 with the cap 22having a through-bore 24 secured to the proximal end of the barrel 14.In keeping with the application, and with reference to FIG. 11, thesyringe 12 further includes a filter 68 secured to the cap 22 interiorof the barrel 14 that covers the opening in the through bore 24 thatcommunicates with the interior of the barrel. The filter 68 is such thatair is considered to be sterile after passing through the filter.

More specifically, the filter 68 is a transducer protector thatinternally contains a hydrophobic and haemophobic membrane with a 0.2micron pore section. Filters with this size of membrane pore areconsidered to be sterility filters and deliver air that is free ofmicrobes above the 0.2 micron size. An exemplary filter is availablefrom GVS S.p.A. of Rome, Italy, as product number TP100ACOG002AA00.

The filter 68 contains a port 70. The port 70 may be chemically bondedto the cap 22 using a solvent, such as cyclohexanone. Alternatively, theport 70 may be secured to the cap by means of screw threads, glue,ultrasonic bonding, or snap fit. In a further alternative, the cap 22may also be configured to receive the filter membrane 68, thuseliminating the separate housing port 70.

The filter membrane 68 could be breached if the flow rate or airpressure rating is exceeded. Thus, the cap 22 and integrated filter 68are preferably configured to allow removal of the cap 22, thuspermitting evaluation of the filter 68 with a test apparatus to confirmthat its integrity was maintained during use. A removable cap would alsopermit direct access to the stopper 20 so that a removable handle couldbe manually attached thereto to move the stopper in the event of afailure of the driver 10. In the illustrated embodiment, the port 70 forthe filter 68 is configured to form a threaded luer lock 72 such that,upon removal of the cap 22 from the syringe 12, a filter integritytester may be attached to the luer lock 72 to check the integrity of thefilter 68.

With reference to FIG. 12, and alternate configuration for the assemblyof the syringe cap 22 and filter 68 is shown in which the filter 68 issecured to the syringe cap by means of a retainer 73, with the assemblybeing secured together by, e.g., ultrasonic shear welding. The syringecap 22 and retainer 73 may be provided with ribs 22 a, 73 a,respectively, for supporting the filter 68.

A stopper, generally designated 20, is slidably received in the barrel14 for movement within the barrel 14 between the first/proximal andsecond/distal ends of the barrel. As best seen in FIG. 14, the stopper20 comprises a plunger head 74 mounted to a piston 76. As illustrated,the piston 76 has a hollow interior sized to receive the luer lock 72 ofthe port 70, thus providing for a maximum volume of the filled syringewhen the stopper 20 is in the fully retracted position. The piston 76 isprovided with a gasket or O-ring 78 that engages the interior wall ofthe barrel 14 that helps to keep the piston 76 aligned with thelongitudinal axis of the syringe. The plunger head 74 is provided withouter edges 80 for sealingly engages the interior wall of the barrel 14.

Optionally, the stopper may include a reflective band 82 to provide foran enhanced IR return signal used for positioning the stopper within thesyringe. The shape of the curvature of the reflective band 82 may beselected to optimize the reflective signal provided by the band 82 tothe sensing elements. Alternatively, the material from which the pistonis made may include reflective pigment additives for this same purpose.

In the event that the pneumatic driver is unavailable, the syringe 12 asdescribed above may be actuated manually without breaking sterility. Forexample, a user can draw non-sterile air into a traditional syringe witha luer fitting, attach it to the cap, and push the plunger on thetraditional syringe to drive the stopper in the sterile syringe. Anysource of pressurized air could similarly be attached to the cap of thesterile syringe to drive the stopper without breaking sterility.Preferably, the inlet to the through bore on the top of the cap isconfigured to receive the tip of a standard syringe.

As illustrated, the through bore 24 terminates in a conical portion 84that is of the same draft angle as ISO 594-1 and 594-2 male and femaleluer sections. This permits the nozzle tip of a syringe to friction fitinside the conical portion 84 to allow the air in the syringe to drivethe stopper 72 in the event of a power failure, thus permitting therecovery of cells trapped in the syringe 12. Alternatively, the cap 22may be formed with a luer lock that extends exterior of the barrel ofthe syringe and defines the inlet to the through bore 24, thus allowingfor other pneumatic systems to be connected without breaching thesterility established by the filter 68.

Thus, an improved pneumatic driver and associated syringe have beendisclosed. The description provided above is intended for illustrativepurposes, and is not intended to limit the scope of the disclosure toany particular method, system, apparatus or device described herein.

1. A disposable syringe comprising: a) an elongated tubular barrelhaving a first end and a second end, the barrel being open on the firstend and tapering to a hollow tip on the second end; b) a cap secured tothe first end of the barrel having a through-bore; c) a filter securedto the cap interior of the barrel and covering an opening in the throughbore interior of the barrel; and d) a plunger head mounted to a pistonand received interior of the barrel, the plunger head engaging aninterior wall of the barrel and being slidable within the barrel betweenthe first and second ends.
 2. The syringe of claim 1 wherein the barrelfurther comprises a collar at the first end and extending laterally fromthe barrel, and the cap is mounted to the collar.
 3. The syringe ofclaim 1 wherein the tip further comprises a luer lock.
 4. The syringe ofclaim 1 wherein the through-bore is configured to receive the tip of asecond syringe.
 5. The syringe of claim 1 wherein the cap furthercomprises a luer lock extending exterior of the barrel and defining anexterior opening in the through-bore.
 6. The syringe of claim 1 whereinthe filter is configured to form a luer lock.
 7. The syringe of claim 1wherein the piston further comprises a hollow interior configured toreceive the luer lock formed by the filter.
 8. The syringe of claim 1wherein the barrel further comprises an annular, inwardly-projectingridge adjacent the first end for sealingly engaging the cap.
 9. Thesyringe of claim 8 wherein the cap comprises an annular,radially-projecting seal for engaging the circumferential,inwardly-projecting ridge at the first end of the barrel.
 10. Thesyringe of claim 1 further comprising a gasket secured to the piston forengaging the interior wall of the barrel.
 11. The syringe of claim 1wherein the cap is removably secured to the barrel.
 12. The syringe ofclaim 1 wherein the cap further comprises a seal encircling an openingin the through bore exterior to the barrel.